High-performance NMR combining β-detection and hyperpolarization for G-Quadruplex structure and dynamics studies

• Applicant: Dr. Beatrice Karg
• Subject Area: Analytical Chemistry
• Term: from 2020 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 441102113

• Final Report Year: 2023

Final Report Abstract

The high-performance NMR measurements at CERN were designed to gain novel insights into the folding of biological macromolecules employing rarely used alkali metal ions as probes. The combination of laser-induced hyperpolarization and resonance detection by asymmetric β-emission yielded significant increases in signal intensity. The project was planned stepwise, starting with a set of vacuum resistant solvents that have been chosen as a tool to explore the capabilities of the method. Measurements on these provided insights both from real-time observation of the implanted nuclei and the unique environments needed for the experimental setup. These results further on proved integral in understanding the environment for the first biological applications of the method with so-called G-Quadruplexes, which are Guanine-rich DNA regions folding into non-canonical structures related to oncogones, cell-aging and therapeutics. A novel dispensing system was implemented for liquid samples to master the challenges posed both by environment and liquid behavior in said environment. This finally allowed for the first measurements of oligonucleotides with β-NMR.

Publications

• 2021, Structural analysis of water in ionic liquid domains – A low pressure study, Journal of Molecular Liquids, 116447
  Dziubinska-Kühn, Pupier, Matysik, Viger-Gravel, Karg, Kowalska
  (See online at https://doi.org/10.1016/j.molliq.2021.116447)
• 2022, Influence of alkali metals on water dynamics inside imidazolium-based ionic liquid nano-domains, Front.Chem., 1028912
  Dziubinska-Kühn, Maddah,Pupier, Matysik, Viger-Gravel, Kowalska, Karg
  (See online at https://doi.org/10.3389/fchem.2022.1028912)
• 2022, Simulations of electric field gradient fluctuations and dynamics around sodium ions in ionic liquids, J. Chem. Phys. 157, 244502
  Gimbal-Zofka, Karg, Dziubinska-Kühn, Kowalska, Wesolowski, Rumble
  (See online at https://doi.org/10.1063/5.0126693)
• 2022, Time-Dependent Hydrogen Bond Network Formation in Glycerol-Based Deep Eutectic Solvents, ChemPhysChem, e202100806
  Dziubinska-Kühn, Pupier, Matysik, Viger-Gravel, Karg, Kowalska
  (See online at https://doi.org/10.1002/cphc.202100806)